Feature-based treatment of depression

Catatonic depression: According to the DSM-IV, the catatonic subtype of depression is characterized by “marked psychomotor disturbance.” This could include an increase or decrease in motor activity, bizarre posturing, or other odd movements. Arguably the most severe subtype, catatonic depression is also associated with extreme negativism, mutism, echolalia, and echopraxia. Research regarding treatment points overwhelmingly to electroconvulsive therapy (ECT), which is recommended as first-line treatment (even prior to pharmacology).7 Modern ECT is usually well-tolerated. There are no absolute contraindications, and ECT can be used in a variety of patients, including those who are pregnant or elderly.1 Availability can be limited, however, especially in rural settings.

Melancholic depression: This subtype is characterized by loss of interest in nearly all activities and not reacting to pleasurable stimuli. A distinct feeling of being depressed, depression that is worse in the morning, early morning awakening, an increase or decrease in motor activity, significant loss of appetite or weight, and excessive or inappropriate guilt are other features of this subtype.

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While a patient experiencing melancholic depression may respond reasonably well to an initial trial of SSRIs, research points elsewhere for effective therapy. Compared with SSRIs, tricyclic antidepressants (TCAs) are more effective for this form of depression.8,9 The side-effect profile of TCAs differs from that of SSRIs and should be weighed on a case-by-case basis prior to starting a trial. Side effects include weight gain and such anticholinergic effects as dry mouth, dry eyes, and constipation. Patients should have an ECG prior to beginning a TCA regimen to detect any underlying heart disease, as TCAs can induce bradyarrhythmias, conduction delays, bundle-branch blocks, and long QT intervals. Use of TCAs with SSRIs, monoamine oxidase inhibitors (MAOIs), certain antibiotics, and a number of other drugs should be closely monitored as blood levels of these drugs can be increased substantially by a concomitant TCA. TCAs can be lethal in overdose, so screening for suicidal ideation is also important. Based on its side-effect profile, nortriptyline (Pamelor) tends to be the most frequently used TCA compared with other drugs in its class.8

Targeting specific symptoms of melancholia may be warranted in some cases. Mirtazapine (Remeron) can improve sleep and appetite. One study found that imipramine (Tofranil) worked better than mirtazapine to improve melancholic symptoms overall. However, patients who used mirtazapine reported significantly improved sleep.10,11 In other studies, mirtazapine resulted in weight gain, a potentially positive side effect in a population that struggles with decreased appetite.11-13 Additionally, mirtazapine may result in a faster resolution of depressive symptoms compared with SSRIs.13

Atypical depression: The presence of mood reactivity is indicative of atypical depression. Other features include significant weight gain or increased appetite, hypersomnia, leaden paralysis, and interpersonal rejection sensitivity.

SSRIs are the treatment of choice.14 They have been tested against both TCAs15 and MAOIs,16 and the effects between drugs did not differ significantly. However, SSRIs were far better tolerated than either the TCAs or MAOIs.

Bupropion (Wellbutrin) may have greater effects than SSRIs in reducing hypersomnia and fatigue.17 Bupropion (Zyban) is commonly used in patients who also wish to stop smoking. Avoid using this drug in patients with a history of seizures or eating disorders because it lowers the seizure threshold.

The link between thyroid function and depression is well-established. Triiodothyronine (T3) is believed to increase serotonergic transmission in the brain. Using T3 to augment antidepressant therapy is supported by research.18-20 One study found that patients with atypical depression improved significantly with T3, while those with melancholic depression actually worsened.20 Persons with lower thyroid function at baseline were more likely to have a greater response to augmentation by T3.

Modafinil (Provigil) can also be used for augmentation of antidepressant therapy. It has been shown to improve overall mood, fatigue, and sleepiness in a number of studies.21-23

Atomoxetine (Strattera), which is indicated for treatment of attention-deficit hyperactivity disorder (ADHD), lacks evidence that it is more effective than SSRIs in reducing depression.24 However, atomoxetine has demonstrated efficacy in lowering the number of binge-eating episodes and could be a useful treatment for those who experience hyperphagia in conjunction with atypical depression.25

Seasonal depression: Depressive episodes recurring in a seasonal pattern are typically seen during winter. Symptoms tend to fall into the atypical category (e.g., weight gain, increased appetite, and sleepiness). Resolution follows with the change of season.

Since symptoms of seasonal depression tend to mirror atypical depression, SSRIs are a good treatment choice. The addition of phototherapy is also recommended. In fact, phototherapy appears to be just as effective as SSRIs in reducing depressive symptoms in patients with seasonal affective disorder and results in fewer adverse effects.26-29 Many patients have been able to prevent the recurrence of depression by beginning phototherapy before the season starts. One adverse effect of phototherapy is the possibility of inducing mania if too much light is used. The effectiveness of phototherapy in nonseasonal types of depression has yet to be established.30

Hormonal depression: This form of depression is often linked to childbirth or menstruation.

  • Postpartum: A distinction must be made between postpartum depression and the “baby blues.” During the first 10 days postpartum, up to 70% of women will experience the baby blues, but the condition will not disrupt functioning. To meet diagnostic criteria, postpartum depression must begin within four weeks of delivery. Symptoms are similar to those of other types of depression and may also include psychosis or anxiety. Women with a history of mood disorder or previous episodes of postpartum depression are at higher risk. SSRIs are generally recommended as first-line treatment.31 The safety of antidepressant therapy during breastfeeding continues to be investigated. Currently any risk to the infant is believed to be low.
  • Premenstrual dysphoric syndrome: This condition is characterized by symptoms that recur during the last week of the luteal phase of the menstrual cycle and diminish within a few days of menstruation onset. At least one of the following symptoms must be present: feeling sad, hopeless, or anxious; mood lability (often with tearfulness); and persistent irritability or anger. Additional symptoms may include decreased interest in normal activities and relationships, difficulty concentrating, lack of energy, changes in appetite and/or sleep, and feeling overwhelmed or suicidal. Physical symptoms may include headaches, breast tenderness, bloating, and muscle or joint pain.

SSRIs remain the treatment of choice for premenstrual dysphoric syndrome.32-35 Furthermore, SSRI therapy may be dose-dependent, with higher doses resulting in greater improvement in mood and irritability.33,34 Treatment can be given daily or only during the 14 days prior to menstruation.

The efficacy of estrogen as an adjunct to antidepressant therapy is debated. One study shows greater reductions in depression in women who took estrogen-containing birth control pills in addition to their antidepressant compared with antidepressants alone.36 Some research suggests that estrogen therapy alone may be sufficient treatment for mood disorders with hormonal etiologies (e.g., postpartum depression and depression during and after menopause).37 Given contradictory findings and the potential risk of exogenous estrogens, more research is needed before estrogen can be recommended as treatment for depression.

Bipolar depression: The use of mood stabilizers for first-line treatment of bipolar disorder is well-established, with lithium being the drug of choice. Other mood stabilizers include anticonvulsants and second-generation antipsychotics. Lamotrigine (Lamictal), in particular, is considered first-line treatment for bipolar depression.38 Valproate (Depacon) is just as effective as lithium in treating mania.39 Carbamazepine and oxcarbazepine (Trileptal) have also been shown to be effective in treating bipolar mania and depression.40-42

For refractory cases of bipolar depression, consider using bupropion in conjunction with a mood stabilizer. Bupropion carries a lower risk of inducing episodes of hypomania or mania than other antidepressants. Compared with sertraline (Zoloft) and venlafaxine (Effexor), bupropion had the lowest rates of switch to mania.43,44 Overall, the use of antidepressants in addition to mood stabilizers is controversial. Antidepressant monotherapy to treat bipolar disorder is clearly contraindicated.